An investigation of the internal motions of alpha-conotoxin GI, a 13-residue, cross-linked peptide, is proposed. The analysis will combine 15N NMR relaxation measurements of the isotopically labeled peptide, from which motional parameters describing the peptide's backbone flexibility will be obtained, and molecular dynamics (MD) simulation, which will provide an atomic-level interpretation of the motions. The work is significant in three respects: (1) It is designed to further our understanding of alpha-conotoxin GI?s interaction with the acetylcholine receptor and the consequent toxicity. (2) This small yet conformationally restricted peptide is an excellent model for developing methods for interpreting NMR motional parameters in terms of mechanical and thermodynamic properties of biological molecules. (3) Characterizing the flexibility of alpha-conotoxin GI may help guide efforts to use it as a drug model. In the first year of the project, the NMR characterization will be carried out. In the second and third years, MD simulations will be performed to address the following issues: What is the quantitative value of the backbone's conformational entropy? Does the pair-wise correlation of bond vector motions affect the calculation of the conformational entropy significantly? With what larger-scale motions are backbone bond vector motions correlated? In addition, restrained MD simulations of unfolded conformers with the disulfide bonds severed are proposed in order to quantify selected contributions of the backbone's conformational entropy to the conformational entropy of folding.